Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 20 S25.4

94 views


Hvidovre Hospital, Copenhagen, Denmark.


Glucagon-like peptide-1 (GLP-1) is an incretin hormone with potent glucose-dependent insulinotropic and glucagonostatic actions. The glucose dependency of its antihyperglycaemic effects minimize any risk of hypoglycaemia. In higher concentrations GLP-1 slows gastric emptying and reduces appetite and food intake, resulting in weight loss. Taken together these actions give GLP-1 an unigue profile as an antidiabetic agents. Since GLP-1 is highly susceptible to enzymatic degradation by dipeptidyl peptidase-4 (DPP-4) strategies for developing GLP-1 as therapeutic agent include DPP-4 resistant GLP-1 analogues and selective DPP-4 enzyme inhibitors to prevent degradation of the peptide.

Treatment with a DPP-4 inhibitor (sitagliptin and vildagliptin) increases intact GLP-1 with a factor 2–4 and improved HbA1c with 0.8–1.0%, without risk for hypoglycaemia. The DPP-4 inhibitor is without gastrointestinal side effects and weight neutral. The GLP-1 analogue exenatide has a half-life of 3–4 h and needed to be administered twice daily before breakfast and dinner. Exenatide improves glycaemic control with an average reduction in HbA1c of about 1.0% and caused a weight loss of 2–3 kg after 30 weeks of treatment. The side effect is primarily nausea during the first days of treatment. Liraglutide, a once daily GLP-1 analogue with a half life of 12 h, reduces HbA1c with 1.0 to 2.0% and weight with 2–4 kg. Liraglutide has been compared with sulfonylurea, rosiglitazon and insulin glargine and in all studies reduction in HbA1c was greater or similar with liraglutide, and weight loss was in favour of liraglutide. At present several GLP-1 analogues for once-weekly administration are in phase 3 development. The final place of incretin-based therapies in the diabetic treatment algorithm will be clarified when we have long-term trials with cardiovascular end-points and data illustrating the effects on beta-cell function and the progression of type 2 diabetes.

Article tools

My recent searches

No recent searches.

My recently viewed abstracts